Iron is an essential mineral and an important component of proteins involved in oxygen transport and metabolism. Iron is also essential in the synthesis of neurotransmitters such as dopamine, norepinephrine, and serotonin. Approximately 15 percent of the body's iron is stored for future needs and mobilized when dietary intake is inadequate. The body usually maintains normal iron status by controlling the amount of iron absorbed from food.

The World Health Organization considers iron deficiency to be the largest international nutritional disorder. Approximately 50% of anemia worldwide is attributable to iron deficiency.

Iron deficiency may be determined by measurement of iron levels within the body, mainly serum ferritin levels, which may also help distinguish between iron deficiency anemia and anemia associated with chronic disease, such as chronic kidney disease (CKD).

There are two forms of dietary iron: heme and nonheme. Sources of heme iron include meat, fish, and poultry. Sources of nonheme iron, which is not absorbed as well as heme iron, include beans, lentils, flours, cereals, and grain products. Other sources of iron include dried fruit, peas, asparagus, leafy greens, strawberries, and nuts.

Vegan and vegetarian diets may increase the risk of deficiencies for certain vitamins and minerals, including iron.

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Iron supplementation has been shown to improve iron status in menstruating women.

B

Iron supplements have been shown to help prevent iron deficiency anemia in pregnant women. Anemia in pregnant women is associated with adverse outcomes such as low birth weight, premature birth, and maternal mortality. Screening by a qualified healthcare provider is needed. Low doses are generally well tolerated and associated with better compliance.

B

According to preliminary data, taking iron orally might improve symptoms of attention-deficit hyperactivity disorder (ADHD). More research is necessary before a conclusion can be drawn.

C

Limited evidence suggests that iron supplementation may reduce the frequency and severity of breath-holding attacks in children. Additional studies are needed to confirm these results.

C

Ferrous sulfate may improve fatigue primarily in women with borderline or low serum ferritin concentrations. Further research is needed to confirm these results.

C

Mixed evidence exists with regard to the effects of iron supplementation on the growth of children. Further research is needed before conclusions can be drawn.

C

Taking iron by mouth seems to improve cognitive function related to iron deficiency in iron-deficient children and adolescents. Further research is needed to confirm the potential benefit of iron in this indication. Iron supplements are not recommended for improving cognitive performance in non-iron-deficient people.

C

Currently, there is a lack of evidence supporting the use of iron to prevent infections in children. Further research is warranted in this area.

C

Iron deficiency may increase the risk of lead poisoning in children. However, the use of iron supplementation in lead poisoning should be reserved for those individuals who are truly iron deficient or for those individuals with continuing lead exposure, such as continued residence in lead-exposed housing.

C

Scientific evidence on the effects of iron on childhood development is conflicting. Some data suggest that iron supplementation primarily promotes psychomotor development, while others suggest more of an influence on intelligence. Further research is needed in this area.

C

Limited evidence suggests that iron supplementation may improve physical performance in children. Further research is needed to confirm these results.

C

Iron supplementation as nutritional support during pregnancy has been studied. Limited evidence suggests that prenatal use of iron, either with folic acid or as part of a multimicronutrient combination, may be beneficial. Further research is needed to determine the specific role of iron for pregnancy support.

C

Preliminary studies suggest that iron supplementation can reverse mild anemia after exercise, improve energy, and enhance performance. However, other studies disagree. Further research is needed in this area before a conclusion can be made.

C

The results of early research indicate that elemental iron can adequately compensate for iron loss in females and males who donate whole blood up to four or six times per year, respectively.

C

Intravenous high-dose iron sucrose therapy in patients with iron deficiency anemia due to gastrointestinal blood loss appears to be safe and therefore is a therapeutic option that may save time and improve patient compliance. More research is needed in this area.

C

Early research reports that iron supplementation following elective hip or knee replacement surgery does not result in higher hemoglobin after surgery or a faster rate of increase in hemoglobin than placebo. However, recent evidence suggests that treatment of preoperative anemia with iron, with or without erythropoietin, reduced the need for blood transfusion and may contribute to improved patient outcomes. Further research is needed.

C

Adequate iron supplementation may be beneficial as an adjunct therapy with erythropoietin in the treatment of predialysis anemia. Predialysis anemia should be treated by a qualified healthcare provider. More research is needed in this area.

C

* Key to grades

A: Strong scientific evidence for this useB: Good scientific evidence for this useC: Unclear scientific evidence for this useD: Fair scientific evidence for this use (it may not work)F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

According to Dietary Reference Intake (DRI) reports developed by the Institute of Medicine's Food and Nutrition Board, the recommended dietary allowance (RDA) for males (19- 50 years old) is eight milligrams daily; for females (19- 50 years old), it is 18 milligrams daily; for adults (51 years old and older), it is eight milligrams daily; for pregnant women (of all ages), it is 27 milligrams daily; and for breastfeeding women (19 years old and older), it is nine milligrams daily.

According to DRI reports developed by the Institute of Medicine's Food and Nutrition Board, the RDA for iron from a completely vegetarian diet should be adjusted as follows: 14 milligrams daily for adult men and postmenopausal women, 33 milligrams daily for premenopausal women, and 26 milligrams daily for adolescent girls.

For increased iron stores, 24 milligrams of iron daily or less in healthy adults did not result in higher iron transport or stores than in those who did not take supplements. However, 32 milligrams of iron daily resulted in higher iron stores than in those taking 24 milligrams daily or less.

For anemia of chronic disease, iron sulfate, fumarate, succinate, and ferritin, ranging from 4-6 milligrams per kilogram to 325 milligrams, has been taken daily by mouth for 2-3 months in patients with chronic kidney disease. Iron sucrose, dextran, gluconate, and ferumoxytol have been injected in the vein, in doses ranging from 72 doses of 31 milligrams, totaling 2,232 milligrams over six months, to 1,020 milligrams in one week.

For iron deficiency anemia, the following doses have been taken by mouth: sodium iron ethylenediaminetetra-acetate (NaFeEDTA), ranging from 4.9 to 10 milligrams daily for up to two years in an iron-deficient population; 120 milligrams of iron daily for three months; 100-975 milligrams of ferrous sulfate daily in divided doses for up to six weeks; 60-120 milligrams of iron proteinsuccinylate (ITF 282), 105 milligrams iron sulfate, or 52.5-105 milligrams of iron polystyrene sulfate daily for 60 days; and average daily doses of approximately 114 milligrams (in women receiving no other nutritional supplementation) and 132 milligrams (in women receiving other supplementation or antimalarial treatment) of elemental iron, for up to 20 weeks or longer. Also, 100-200 milligrams of iron dextran, 200 milligrams of iron sucrose, 125 milligrams of iron gluconate, and 20-200 milligrams of iron saccharate have been injected into the vein for six weeks.

For mental performance (infant and childhood development), 20 milligrams of elemental iron has been taken daily by mouth, from the 20th week of gestation until delivery, in pregnant women.

For prevention of iron deficiency anemia in pregnancy, the following doses have been taken daily by mouth: 20-50 milligrams of elemental iron for up to 28 weeks of pregnancy; 60-124 milligrams of iron daily; 27-225 milligrams of elemental iron daily; 60 milligrams of elemental iron every three days; and 160 milligrams every week.

Children (younger than 18 years)

According to DRI reports developed by the Institute of Medicine's Food and Nutrition Board, the RDA is 11 milligrams for infants 7-12 months old, seven milligrams for children 1-3 years old, 10 milligrams for children 4-8 years old, eight milligrams for children 9-13 years old (male and female), 11 milligrams for males 14-18 years old, 15 milligrams for females 14-18 years old, 27 milligrams for pregnant females 14-18 years old, and 10 milligrams for breastfeeding females 14-18 years old. For infants 0-6 months old, 0.27 milligrams is the adequate intake level (AI), which is used when the RDA cannot be determined.

For anemia of chronic disease, iron dextran, iron sucrose, or sodium ferric gluconate, at 0-7 milligrams per kilogram per week; four milligrams per kilogram per dose, for 10 doses; 1.5-8.8 milligrams per kilogram per dose, for 1-8 doses; one milligram per kilogram per week; 31.25-125 milligrams per week; 100 milligrams per dose, for two doses per month; 45 milligrams per square meter per week for 10 weeks; 100 milligrams per dose, for 6-10 doses; and 25-100 milligrams per dose, for 10 doses in children undergoing hemodialysis, have been injected into the vein.

For breathing problems (breath-holding attacks), ferrous sulfate solution at five milligrams per kilogram has been used daily by mouth for 16 weeks.

For growth, the following doses have been taken by mouth: 1.3-10 milligrams per kilogram iron for up to 52 weeks; 10-60 milligrams of iron for 8-52 weeks; and 15-80 milligrams daily, 15 milligrams weekly, 1.2 milligrams per liter (formula), and 1-3 milligrams per kilogram daily, for 2-15 months.

For improving cognitive performance related to iron deficiency, 2-4 milligrams of elemental iron per kilogram daily, 17-260 milligrams of elemental iron daily, or 60 milligrams of elemental iron weekly has been taken by mouth for up to 29 weeks.

For infections, the following doses have been taken by mouth: 10-200 milligrams daily, 2-6 milligrams per kilogram daily, and 15 milligrams weekly; and fortified doses of 7.5-40 milligrams per 100 milligrams, and 6.5-12 milligrams per liter, for up to 18 months. Parenteral doses of 50-150 milligrams iron have been taken for up to 10 months.

For iron deficiency anemia, 1-5 milligrams per kilogram to 10-60 milligrams of iron, given daily or weekly from one week to 12 months, have been taken by mouth.

For mental performance (infant and childhood development), daily ferrous sulfate dosages of one milligram per kilogram for three months, 7.5 milligrams for five months, and 10 milligrams for six months have been taken by mouth. Iron-fortified formulas of 1.2 milligrams per liter and 12.8 milligrams per liter for 9-15 months have been taken by mouth. Iron doses of 10-60 milligrams daily, 2-6 milligrams per kilogram daily, and 1.2-12.8 milligrams per liter (fortified cereal or milk) for up to 16 months, have been taken by mouth. Parenteral doses of 50 milligrams (duration and frequency information not provided) have also been used.

For physical performance enhancement in children, 30-40 milligrams, 60 milligrams, and 200 milligrams of iron have been taken daily by mouth for 1-2 months.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Avoid with known allergy/hypersensitivity to products containing iron. Contact hypersensitivity to iron has been reported.

Side Effects and Warnings

According to DRI reports developed by the Institute of Medicine's Food and Nutrition Board, the tolerable upper limit (UL) for adults (19 years old and older, including pregnant and nursing mothers) is 45 milligrams daily. According to DRI reports developed by the Institute of Medicine's Food and Nutrition Board, the UL for infants (1-12 months) is not possible to establish, the UL for children (1-13 years old) is 40 milligrams daily, and the UL for adolescents (14-18 years old) is 45 milligrams daily.

Increased body iron stores may increase the risk of cancer or general mortality.

Occupational exposure to iron or iron fumes may put workers at a higher risk for various diseases, including neurological disease and cancers.

Hemoconcentration (increased concentration of blood cells due to loss of plasma or water from the bloodstream) has been reported.

Correcting hematocrit and hemoglobin levels in chronic kidney disease (CKD) may increase thrombovascular events and mortality. The role of iron in these events is unclear.

Some evidence suggests a connection between iron status and coronary heart disease risk.

Discoloration of the urine may occur with iron supplementation. Darkening of the stools may also occur.

In malaria-endemic populations, increased episodes of dysentery (severe diarrhea), as well as an increase in illness due to infections, have been reported.

Increased risk of hospitalization due to severe illness has been reported following use of iron and folic acid.

Although not well studied in humans, a single life-threatening event after intravenous administration of sodium ferric gluconate complex (SFGC) has been reported.

Oral iron preparations may possibly blacken or stain teeth.

Use cautiously in people with a history of kidney disease, intestinal disease, enteritis, colitis, pancreatitis, or hepatitis; and in those who consume excessive alcohol, plan to become pregnant, or are over age 55 and have a family history of heart disease. These patient populations should consult a healthcare provider before taking iron.

Use cautiously in pregnancy for elevating iron stores in bone marrow, as the U.S. Food and Drug Administration (FDA) has recognized iron as Pregnancy Category C for this use.

Use cautiously in uremic patients treated with dialysis, as uncontrollable sweating has been reported with long-term iron supplementation in such patients.

Use cautiously in patients with gastrointestinal disorders, as nausea, vomiting, heartburn, abdominal pain, constipation, and diarrhea have been reported. A case of iron-induced gastric mucosal injury following long-term use has also been reported.

Avoid in patients with or at risk for iron overload, due to hematochromatosis (a disorder that results in too much iron being absorbed from the gastrointestinal tract, often genetic) or any other cause. The most commonly associated early hemochromatosis symptoms include lethargy, arthralgia (pain in joints), and loss of libido (sex drive). Those with more severe disease may develop liver fibrosis or cirrhosis (which may progress to cancer if untreated), arthritis, gonadal failure, diabetes mellitus, cardiac failure, and arrhythmias (altered heart rhythm).

Avoid in individuals with hemolytic anemia.

Avoid with known allergy/hypersensitivity to products containing iron.

Pregnancy and Breastfeeding

Pregnant or breastfeeding women should seek guidance from a qualified healthcare provider before taking dietary supplements. The iron status of the pregnant woman should be measured early (before the 15th week of gestation), and iron supplements should be given as selective prophylaxis based on the serum ferritin level.

The FDA has categorized iron as a Pregnancy Category B drug in general. However, iron is recognized as Pregnancy Category C when used for replenishing depleted iron stores in bone marrow, as safety for this use during pregnancy has not been established.

Acetohydroxamic acid (AHA, Lithostat®) is prescribed to decrease urinary ammonia and may help with antibiotics to work or help with other kidney stone treatment. Use with iron supplements may cause either medicine to be less effective.

Allopurinol (Zyloprim®), a medication used to treat gout, may increase iron storage in the liver.

Aminosalicylic acid (para-aminosalicylic acid; PAS, Paser) may cause a malabsorption syndrome (weight loss, iron and vitamin depletion, excessive fat in the stools (steatorrhea)). A qualified healthcare provider should be contacted immediately if any of these symptoms are present.

Iron has been found to decrease the absorption of fluoroquinolone and tetracycline antibiotics. Fluoroquinolones include ciprofloxacin (Cipro®), levofloxacin (Levaquin®), ofloxacin (Floxin®), and others. Some of the tetracycline antibiotics include doxycycline (Vibramycin®), minocycline (Minocin®), and tetracycline (Achromycin®).

Regular use of aspirin may contribute to iron deficiency in the elderly.

Preliminary research has shown that concurrent iron administration inhibits the absorption of clodronate, a bisphosphonate drug.

Chloramphenicol (Chloromycetin®) can reduce the response to iron therapy in iron deficiency anemia.

Cholestyramine (Questran®) may bind iron in the gut and reduce its absorption.

Iron supplements and dimercaprol may combine in the body to form a chemical that is harmful to the kidneys.

H2 blockers such as cimetidine (Tagamet®), ranitidine (Zantac®), famotidine (Pepcid®), or nizatidine (Axid®) may reduce iron absorption. According to expert opinion, iron supplements are not usually required unless high doses of H2 blockers are being used.

Desferrioxamine and deferiprone are both iron-chelating drugs that lower iron levels.

There is some evidence in healthy people that iron forms chelates with levodopa (Sinemet®) and reduces the amount of levodopa absorbed.

Iron can decrease the absorption and efficacy of levothyroxine (Levoxyl®, Synthroid®) by forming insoluble complexes in the gastrointestinal tract.

Iron can decrease the absorption of methyldopa (Aldomet®), resulting in increases in blood pressure.

Some evidence suggests that oral iron supplements markedly reduce absorption of mycophenolate mofetil (CellCept®). However, other studies suggest that mycophenolate pharmacokinetics is not affected by iron supplementation.

NSAIDs, such as ibuprofen (Advil®), naproxen (Aleve®), or ketorolac (Toradol®), may cause mucosal damage and bleeding throughout the gastrointestinal tract. Chronic blood loss associated with long-term use of these agents may contribute to iron deficiency anemia. Iron-rich food intake may be advised as an alternative.

There is some evidence that pancreatic enzyme supplements, such as Cotazym®, Creon®, Pancrease®, Ultrase®, and Viokase®, may reduce iron absorption and contribute to iron deficiency.

Intake of vitamin A along with iron may enhance the response to iron supplements, possibly by increasing iron absorption. Iron and zinc supplementation have also been shown to improve vitamin A status in children. However, other evidence suggests that iron may cause vitamin A deficiency. The amount of vitamin C in the diet is a factor in dietary iron absorption and iron status.

Joint supplementation with iron and zinc may result in less absorption of the minerals than supplementing each agent alone. Iron supplementation in pregnancy may reduce serum zinc levels. However, in iron-replete women, iron supplementation increases zinc absorption later in pregnancy. Supplementing iron in ileostomy patients has also been shown to inhibit zinc absorption. Theoretically, zinc supplementation may inhibit iron transport via decreased copper absorption.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.